C. difficile is the major infectious cause of nosocomial diarrhea, causing as many as 25% of cases of nosocomial diarrhea. C. difficile infection (CDI) is increasing in incidence and severity, affects 500,000 Americans each year, causes 20,000 deaths annually, and imposes a significant financial burden on healthcare institutions - $1.1 billion annually in the U.S. Prevention of Clostridium difficile is a national priority and a numbe of evidence-based preventive strategies such as appropriate diagnostic testing, hand hygiene, contact isolation, empiric isolation and environmental disinfection may help to reduce the burden of C. difficile infection (CDI). However, implementation of these CDI prevention strategies-the CDI bundle- is highly variable across institutions. Our ability to successfully implement preventive strategies for CDI is hampered by a limited understanding of factors influencing the adoption of of this CDI bundle. We hypothesize that a number of work system barriers may pose challenges to successful acceptance, adoption, and implementation of the CDI bundle. Our objective is to assess work system barriers and facilitators to bundle implementation using a mixed-methods approach. We will undertake direct observations of practices relevant to CDI prevention; conduct focus groups of healthcare workers (HCWs); and use vignettes to examine HCW perceptions, attitudes, & decision-making about CDI prevention. We will use the innovative Systems Engineering Initiative for Patient Safety (SEIPS) model of work system and patient safety as the study framework. Immediate benefits of achieving the objectives of this proposal will be generation of important data regarding barriers and facilitators of implementation using a systems engineering approach. This is among the first research studies to systematically examine barriers and facilitators of implementation of a prevention bundle for CDI. Our project is innovative in that it will employ the SEIPS framework to undertake a complete work systems analysis for CDI prevention; use a number of complementary approaches to data collection; and consider not just HCWs involved in direct patient care, but also ancillary staff who are critical to successful CDI prevention. Our study methods and approach may be widely used not just for CDI but also other HAIs, and will add to the fields of patient safety and infection control.